The overall aim of this research is to critically evaluate the functional properties and utility of monoclonal antibodies to surface structures on human lung carcinoma cells with three primary objectives in mind. These are: (1)\to use murine monoclonal antibodies to assess any quantitative differences among cell surface molecules expressed on different histological types of non-small cell bronchogenic carcinoma, autochthonous lymphoblastoid and fibroblast cells and other carcinoma cells not of lung origin; (2)\to critically evaluate the utility of such monoclonal antibodies in controlling growth and metastatic properties of lung tumor cells; and (3)\to assess the ability of monoclonal antibodies to effect the killing of lung tumor cells in vivo and to delineate the mechanism(s) involved in this process. Among specific aims planned to achieve these objectives is to implement an existing panel of monoclonal antibodies with a second generation of antibodies directed to different epitopes to enhance their affinity and optimize their functional utility in affecting tumor growth and proliferation. Fluorescence-activated cell sorter analysis and saturation binding studies with Scatchard plot evaluations will be used in a concerted effort to clearly distinguish those functional cell surface structures that are preferentially expressed on non-small cell bronchogenic carcinoma cells. Also determined will be the effect of blocking surface antigens with monoclonal antibody on spreading and adhesion of lung tumor cells to endothelial cell monolayers. Finally, monoclonal antibodies directed to lung tumor cell membrane antigens which are not shed will be critically evaluated as to their efficacy in killing human lung tumor cells in vivo in athymic (nu/nu) mice, and a concerted effort will be made to determine the mechanism(s) involved in these phenomena. It is anticipated that results from such studies will contribute to a better basic understanding of human neoplasms and help to pave the way for the design of new and effective approaches to be used in the clinical attack on human lung cancer.